Abstract

Inflammasomes coordinate the maturation of IL-1β and IL-18 in response to danger signals. They are vital for maintenance of intestinal homeostasis and have been linked to chronic intestinal inflammation in humans. Probiotics have been advocated as treatment in intestinal inflammation. So far, no study has investigated the role of the inflammasome in canine chronic enteropathy (CE). In this study the intestinal expression of inflammasome components was assessed in CE dogs compared to controls, when treated with probiotic Enterococcus faecium (EF) ex-vivo and in-vivo. RNA extraction from endoscopic biopsies and reverse-transcriptase quantitative PCR was performed for NLRP3, casp-1, IL-1β and IL-18. Immunohistochemistry was performed to investigate protein expression in tissues. Gene expression of casp-1 and NLRP3 was lower in CE samples than controls. Ex-vivo treatment with EF reduced NLRP3 expression in control samples. Treatment of CE dogs with EF alongside dietary intervention had no effect on gene expression. In contrast, IL-1β protein expression in CE decreased with dietary treatment (but not with probiotics). The results of this study suggest that the inflammasome or its components may be partially involved in the inflammatory process seen in CE, but distinct from intestinal inflammation in humans.

Highlights

  • In dogs, chronic enteropathies (CE) are a group of disorders of unknown cause associated with chronic gastrointestinal (GI) symptoms of unknown cause [1]

  • Due to the absence of more suitable antibodies, this was mostly done by assessing transcription levels using quantitative reverse-transcription Polymerase chain reaction (PCR), and by IHC to assess protein production for selected components

  • No NLRP1 mRNA expression was detected in duodenal samples from healthy and CE dogs, which might imply that this gene does not play a major role in the innate immune mechanisms in the canine gut

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Summary

Introduction

Chronic enteropathies (CE) are a group of disorders of unknown cause associated with chronic gastrointestinal (GI) symptoms of unknown cause [1]. There are parallels to human Inflammatory Bowel Disease (IBD), as both are considered chronic immune-mediated inflammatory diseases of the GI tract that result from a dysregulated mucosal immune response to bacterial antigens [2]. Inflammasomes are found in a wide range of cell types including macrophages, dendritic cells and intestinal epithelial cells [3]. The inflammasome complex is composed of multiple cytosolic proteins, including NOD-like receptors (NLRs), the adaptor protein ASC. Effect of Probiotics on the Canine Intestinal Inflammasome

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